Since cytomegalovirus (CMV) is the leading cause of congenital infections in this country and since damaging fetal infections are more likely to result from primary maternal infection during pregnancy than from a recurring infection, then it is assumed that prevention of morbidity due to congenital CMV will be most successfully accomplished through an immunization program aimed at preventing primary maternal infections. However, before this can be undertaken it must first be determined to what extent prior CMV infection in the normal host prevents reinfection with new strains of virus. We propose to determine the rate of primary CMV infection among day care workers and define risk factors for seroconversion in this group; in addition, we will determine whether children in day care centers with high rates of CMV infection are reinfected with new strains of virus. Longitudinal virologic and serologic studies of day care workers from 35 centers will provide information for defining risk factors for primary CMV infection in this group, such as age of children attended, total hours worked per week, size of day care center, and contact with children known to be excreting CMV. Restriction enzyme analysis of viral isolates will be used to provide laboratory confirmation of horizontal transmission of CMV from children to workers. Children in three day care centers with high rates of CMV infection will be followed longitudinally to determine if any are being reinfected with new viral strains. This will be accomplished by collecting multiple isolates from both urine and saliva over time and using restriction enzyme analysis and hybridization with CMV DNA probes to compare isolates. Seropositive day care workers will be followed in a similar manner, with serial testing for CMV excretion in saliva and urine and restriction enzyme analysis to determine if reinfection with new strains can be detected. By examining this population of normal hosts and determining to what degree natural infection protects from reinfection, knowledge will be acquired that will be critical in assessing a potential candidate vaccine.